Recombinant human growth hormone (GH)-binding protein enhances the growth-promoting activity of human GH in the rat.

To address the role of the GH-binding protein (GHBP) in GH physiology, two forms of recombinant human GHBP (rhGHBP) were given alone or in combination with rhGH to hypophysectomized rats or GH-deficient dwarf rats. Hypophysectomized rats were given daily sc injections of excipient, hGH, rhGHBP, or rhGH plus rhGHBP (produced in Escherichia coli) for 7 days. Injections of rhGH induced dose-related body weight gain and bone growth that were increased by the coadministration of rhGHBP with rhGH; rhGHBP alone had no effect. Serum insulin-like growth factor increased 24 h later when rhGH was given together with rhGHBP (P < 0.01), but not when rhGH was given alone. E. coli-derived rhGHBP also enhanced the bioactivity of coadministered rhGH in the GH-deficient dwarf rat. In contrast, the glycosylated rhGHBP, made in human A293 cells, inhibited the growth-promoting activity of coadministered rhGH. The opposite effects of these two forms of rhGHBP could be explained by clearance studies that showed radiolabeled rhG...